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BACKGROUND: Spirometric Z-scores from the Global Lung Initiative (GLI) rigorously account for age-related changes in lung function and are thus age-appropriate when establishing spirometric impairments, including a restrictive pattern and air-flow obstruction. However, GLI-defined spirometric impairments have not yet been evaluated regarding associations with static lung volumes (total lung capacity [TLC], functional residual capacity [FRC], and residual volume [RV]) and gas exchange (diffusing capacity). METHODS: We performed a retrospective review of pulmonary function tests in subjects >40 y old (mean age 64.6 y), including pre-bronchodilator measures for: spirometry (n = 2,586), static lung volumes by helium dilution with inspiratory capacity maneuver (n = 2,586), and hemoglobin-adjusted single-breath diffusing capacity (n = 2,508). Using multivariable linear regression, adjusted least-squares means (adjLSMeans) were calculated for TLC, FRC, RV, and hemoglobin-adjusted single-breath diffusing capacity. The adjLSMeans were expressed with and without height-cubed standardization and stratified by GLI-defined spirometry, including normal (n=1,251), restrictive pattern (n=663), and air-flow obstruction (mild, [n=128]; moderate, [n = 150]; and severe, [n = 394]). RESULTS: Relative to normal spirometry, restrictive-pattern had lower adjLSMeans for TLC, FRC, RV, and hemoglobin-adjusted single-breath diffusing capacity (P < .001). Conversely, relative to normal spirometry, mild, moderate, and severe air-flow obstruction had higher adjLSMeans for FRC and RV (P < .001). However, only mild and moderate air-flow obstruction had higher adjLSMeans for TLC (P < .001), while only moderate and severe air-flow obstruction had higher adjLSMeans for RV/TLC (P < .001) and lower adjLSMeans for hemoglobin-adjusted single-breath diffusing capacity (P<.001). Notably, TLC (calculated as FRC= inspiratory capacity) was not increased in severe air-flow obstruction (P > .11) because inspiratory capacity decreased with increasing air-flow obstruction (P < .001), thus opposing the increased FRC (P < .001). Finally, P values were similar whether adjLSMeans were height-cubed standardized. CONCLUSIONS: A GLI-defined spirometric restrictive pattern is strongly associated with a restrictive ventilatory defect (decreased TLC, FRC, and RV), while GLI-defined spirometric airflow obstruction is strongly associated with hyperinflation (increased FRC) and air trapping (increased RV and RV/TLC). Both spirometric impairments were strongly associated with impaired gas exchange (decreased hemoglobin-adjusted single-breath diffusing capacity). [ABSTRACT FROM AUTHOR]